ObjectivesWe report the disease-specific survival of patients with human papillomavirus (HPV)-associated and HPV-independent vulvar squamous cell carcinomas and determine whether differences exist and are independent of stage and age at diagnosis.MethodsThis was a retrospective cohort study with case note and pathology slide review of 265 consecutive women with vulvar squamous cell carcinoma. These patients were treated over a 15 year period (2001–2016) at a centralized cancer center covering half the population of New Zealand. The women’s cancers were categorized dependent on their adjacent pathology, immunohistochemistry and HPV status following expert slide review. Disease-specific survival was calculated using Kaplan-Meier univariable and Cox proportional hazard (adjusting for stage, age, and HPV dependence) multivariable methods.ResultsThe survival analysis included 236 women with follow-up to 96 months; 124 of them were HPV-associated, 95 HPV-independent, and 17 were unclassifiable. Of the 236 women, 146 were stage 1 (92 HPV-associated, 49 HPV-independent, 5 unclassifiable), 13 stage II (7 HPV-associated, 6 HPV-independent), 62 stage III (20 HPV-associated, 34 HPV-independent, 8 unclassifiable) and 15 stage IV (5 HPV-associated, 6 HPV-independent, 4 unclassifiable). HPV-independent vulvar squamous cell carcinomas had significantly worse survival than HPV-associated vulvar squamous cell carcinomas independent of stage and age at diagnosis (HR 3.6 (95% confidence interval (CI): 1.6 to 8.2)). Tumors that were unclassifiable by HPV type also had significantly worse survival than HPV-associated tumors independent of stage and age at diagnosis (HR 6.2 (95% CI: 2.4 to 16.0)).ConclusionsHPV-independent vulvar squamous cell carcinomas present more frequently in older women than HPV-associated tumors. However, the poorer prognosis is independent of age and stage, with worse outcomes even in early stage disease.